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目的探讨99Tcm标记血管内皮生长因子受体2(vascular endothelial growth factor receptor-2,VEGFR-2,KDR)小分子拮抗肽K237的方法,研究标记物在健康动物体内的药代动力学特性及体内分布特点。方法化学方法合成制备MAG3-K237,并用99Tcm标记;鉴定标记物的理化性质;测定标记物经新西兰大白兔静脉注射后不同时相血液放射性浓度,得出最佳房室模型与药代动力学参数;分别测定经尾静脉注射7.4MBq标记物后的昆明小鼠各器官质量和放射性计数,经参考源校正后计算各脏器每克组织百分注射剂量率(%ID/g);经耳缘静脉注射37MBq标记物,在SPECT下观察其在兔体内的动态分布。结果99Tcm-MAG3-K237的放化纯度为(97.98±0.76)%,比活度为(3.54±0.03)TBq/mmol;室温(25℃)下保存8h后放化纯度为(96.15±0.37)%;半胱氨酸置换率为0.2%～0.37%;不与血清蛋白结合;兔体内动力学过程符合权重为1/c2的三室模型,快分布相半衰期(t1/2α)、慢分布相半衰期(t1/2β)及消除相半衰期(t1/2γ)分别为(4.00±3.53)、(24.48±9.84)、(852.24±444.00)min,清除率(CL)为(1.833±0.408)ml/min;标记物在健康小鼠体内清除迅速,肾脏、肝脏及肠道分布较多,但肝脏30min后分布很少。结论本研究制备的99Tcm-MAG3-K237的放射化学纯度高,体内外稳定性好,血液清除速度快,通过肾脏和肝脏双重途径代谢。
Objective To investigate the method of 99Tcm labeling of small molecule antagonist peptide K237 of vascular endothelial growth factor receptor-2 (VEGFR-2, KDR) to study the pharmacokinetics and in vivo distribution of the marker in healthy animals Features. METHODS: MAG3-K237 was synthesized by chemical method and labeled with 99Tcm. The physical and chemical properties of the marker were identified. The radioactive concentration of the marker was measured at different time points after intravenous injection of New Zealand white rabbits. The best compartment model and pharmacokinetic parameters . The organ weight and radioactivity count of Kunming mice after 7.4MBq injection of tail vein were measured respectively. The percentage of injected dose per gram of tissue (% ID / g) was calculated after reference source correction. Intravenous injection of 37MBq markers in SPECT to observe its dynamic distribution in rabbits. Results The radiochemical purity of 99Tcm-MAG3-K237 was (97.98 ± 0.76)% and the specific activity was (3.54 ± 0.03) TBq / mmol. The radiochemical purity of 99Tcm-MAG3-K237 was (96.15 ± 0.37)% after stored at room temperature ; The cysteine exchange rate was 0.2% -0.37%; it was not bound to serum protein. The in vivo kinetics of rabbits conformed to the three-compartment model with a weight of 1 / c2, the fast phase half-life (t1 / 2α), slow phase half-life t1 / 2β and t1 / 2γ were (4.00 ± 3.53), (24.48 ± 9.84) and (852.24 ± 444.00) min respectively, and the clearance rate was (1.833 ± 0.408) ml / min. The objects were rapidly cleared in healthy mice with more distribution of the kidney, liver and intestine, but the distribution of the liver after 30 minutes was very little. Conclusion 99Tcm-MAG3-K237 prepared in this study has high radiochemical purity, good in vitro and in vivo stability, fast blood clearance, and is metabolized by both renal and hepatic pathways.